The University of Southern California (USC) Tobacco Center of Regulatory Science (TCORS) addresses the cross-cutting theme of tobacco use among vulnerable populations, proposing an agenda of methods development and research that will help to assure that the activities of the Food and Drug Administration (FDA) reach to the diverse groups at risk for nicotine addiction and the adverse consequences of tobacco use. The proposed USC TCORS directly responds to RFA-DA-13-003 with a highly experienced multi- disciplinary team of investigators who already work together on tobacco research with populations considered vulnerable to tobacco use and nicotine addiction. There are three overall research aims of this TCORS: 1) evaluate marketing, social influence, social media, and network influences on tobacco use and product choice, emphasizing vulnerable populations, with the ultimate aim of identifying ways to reverse or counteract these influences; 2) examine tobacco product distribution and regulation among local vendors, whose stores are a key point for purchase, contact with industry marketing and promotion, and regulatory education initiatives; 3) examine different topographies of tobacco use, integrating phenotypic variables with personal, social, cultural and environmental variables to determine how future tobacco control initiatives may be tailored to different vulnerable groups. These aims are met through three Research Projects which have overiapping elements: 1) internet-based investigation of marketing and social media influences drawn from diverse populations; 2) a study of small tobacco retailers in California and the impact of community environment and local regulatory campaign efforts on both vendor practices and consumer behavior; 3) a study of tobacco use trajectories and use topography in an established population-based cohort. This theory- based research acknowledges the dynamic interplay between tobacco regulatory, control, and industry systems as they affect tobacco use in vulnerable populations. The USC TCORS will have five cores: Methods, Population, Pilot Programs, Training and Education, and Administrative. The latter will be responsible for overall coordination and integration of research, training, and core activities; communication with other TCORSs, and dissemination of findings. All of the research studies and cores are designed to promote tobacco regulatory science as a discipline, support research and collaboration within and across other TCORSs, and advance new research questions and methods. The USC TCORS is expected to provide evidence that will enhance the FDA's capacity to impact on public health through tobacco regulation. RELEVANCE (See instructions): The USC Tobacco Center of Regulatory Science (TCORS) focuses on populations that are at high-risk for use of tobacco products and addiction in order to help the FDA reduce tobacco use and its disease burden. Addressing FDA priorities, researchers will examine social media and small retailers as ways that the tobacco industry reaches vulnerable populations, and how eariy smoking patterns predict tobacco product use and addiction. The TCORS will generate new research and training methods for regulatory science.